p-Chlorophenylalanine and fluoxetine inhibit D-fenfluramine-induced Fos expression in the paraventricular nucleus, cingulate cortex and frontal cortex but not in other forebrain and brainstem regions.
D-Fenfluramine, a putative serotonin releaser and reuptake inhibitor, is commonly prescribed for the treatment of obesity. Brain sites activated by D-fenfluramine have been mapped via the expression of the immediate early gene Fos. However, it is not clear that serotonin release in the brain mediates the effects of D-fenfluramine on Fos expression. The present study determined whether D-fenfluramine induces the expression of Fos in the brain through the release of serotonin. Rats were pretreated either with the serotonin depleting drug p-chlorophenylalanine (PCPA) or with the serotonin reuptake inhibitor fluoxetine. Both drugs inhibited D-fenfluramine-induced Fos expression in the cingulate cortex, frontal cortex, and the parvocellular subdivision of the paraventricular nucleus of the hypothalamus. Neither drug reduced D-fenfluramine-induced Fos responses in several other brain areas, including the caudate-putamen, amygdala, and brainstem regions such as the lateral parabrachial nucleus and nucleus of the solitary tract. These results indicate regional specificity of mechanisms mediating D-fenfluramine-induced Fos expression. It is likely that D-fenfluramine-induced Fos expression at various sites in the brain is mediated via a combination of serotonin release and other, as yet unidentified, neurotransmitters.
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Department of Cell Biology, Neurobiology and Anatomy, Loyola University of Chicago School of Medicine, Maywood, IL 60153, USA.
Van De Kar
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Gray
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D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D010134:Fenclonine / Q000494:pharmacology*; D005277:Fenfluramine / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D005625:Frontal Lobe / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018490:Serotonin Agents / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D001067:Appetite Depressants; D010134:Fenclonine; D005277:Fenfluramine; D005473:Fluoxetine; D016760:Proto-Oncogene Proteins c-fos; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors